The subject matter disclosed herein relates to the use of microbubble compositions in diagnostic or therapeutic applications.
A variety of therapeutic agents or drugs are not commercially or medically viable due to one or more of adverse side effects, poor solubility in blood, or high cost. To address certain of these failings, delivery systems such as ultrasound microbubble (USMB) mediated delivery systems have been developed. In such a system, a gas-filled microbubble is associated with a treatment agent of interest. Under treatment conditions, the gas-filled microbubbles undergo cavitation in response to the application of ultrasonic energy at a targeted site (i.e., anatomic region) of interest. This cavitation event results in microbubble destruction (inertial cavitation) and is, presumably, accompanied by a shock wave that leads to the formation of transient pores in the membranes of surrounding tissues and cells. The transient pores allow the treatment agent to gain access to the tissues to be treated. In other scenarios, ultrasound results in stable cavitation rather than inertial cavitation, which can also lead to enhanced delivery of drugs to tissues or cells. Such approaches have been investigated with possible future applications involving the targeted delivery of small molecule drugs, oligonucleotides, and plasmid DNA (pDNA), such as to a patient.
Delivery of therapeutic agents can be significantly enhanced in the presence of microbubbles upon application of ultrasound. Generally, agent pharmacokinetic properties and clearance mechanisms are key drivers behind delivery to tissue and cells. Binding between the microbubble and the agent of interest can affect the efficiency of agent delivery to a site of interest by, for example, enhancing in vivo stability, manipulating agent biodistribution characteristics, or other mechanisms. The nature and extent of such binding relationships, and their effect on delivery, however, have generally not been thoroughly researched and are poorly understood. It may be desirable, therefore, to develop a more suitable USMB mediated drug delivery system and associated delivery agents.